rs34089864

Variant names:

• chr11-116790052-G-A
• rs34089864
• NM_001371904.1:c.*76C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001371904.1(APOA5):​c.*76C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 1,504,408 control chromosomes in the GnomAD database, including 1,436 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (185 hom., cov: 34)
  • Exomes 𝑓: 0.027 (1251 hom.)
• Consequence: APOA5 NM_001371904.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461
• Publications: 11 publications found

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

APOA5 Gene-Disease associations (from GenCC):

• hypertriglyceridemia 1

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hyperlipoproteinemia type V

  Inheritance: AD, SD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOA5	NM_001371904.1	c.*76C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000227665.9	NP_001358833.1
APOA5	NM_001166598.2	c.*76C>T		3_prime_UTR_variant	Exon 4 of 4		NP_001160070.1
APOA5	NM_052968.5	c.*76C>T		3_prime_UTR_variant	Exon 4 of 4		NP_443200.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA5	ENST00000227665.9	c.*76C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001371904.1	ENSP00000227665.4
APOA5	ENST00000433069.2	c.*76C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000399701.2
APOA5	ENST00000542499.5	c.*76C>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000445002.1
APOA5	ENST00000673688.1	c.*76C>T		downstream_gene_variant				ENSP00000501141.1

Frequencies

GnomAD3 genomes AF: 0.0377 AC: 5734 AN: 152174 Hom.: 182 Cov.: 34

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0538

Gnomad FIN AF: 0.0481

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0269 AC: 36431 AN: 1352116 Hom.: 1251 Cov.: 24 AF XY: 0.0283 AC XY: 18986 AN XY: 671854

African (AFR) AF: 0.0462 AC: 1426 AN: 30842

American (AMR) AF: 0.0387 AC: 1447 AN: 37384

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 754 AN: 24958

East Asian (EAS) AF: 0.195 AC: 7072 AN: 36278

South Asian (SAS) AF: 0.0616 AC: 4892 AN: 79470

European-Finnish (FIN) AF: 0.0455 AC: 2284 AN: 50198

Middle Eastern (MID) AF: 0.0432 AC: 222 AN: 5140

European-Non Finnish (NFE) AF: 0.0160 AC: 16515 AN: 1031292

Other (OTH) AF: 0.0322 AC: 1819 AN: 56554

GnomAD4 genome AF: 0.0377 AC: 5747 AN: 152292 Hom.: 185 Cov.: 34 AF XY: 0.0412 AC XY: 3071 AN XY: 74466

African (AFR) AF: 0.0466 AC: 1937 AN: 41570

American (AMR) AF: 0.0512 AC: 784 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3466

East Asian (EAS) AF: 0.139 AC: 719 AN: 5178

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4826

European-Finnish (FIN) AF: 0.0481 AC: 510 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1339 AN: 68020

Other (OTH) AF: 0.0393 AC: 83 AN: 2112

Alfa AF: 0.0263 Hom.: 24

Bravo AF: 0.0362

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34089864; hg19: chr11-116660768; COSMIC: COSV57064776; COSMIC: COSV57064776;